Malaysia Airlines said in a statement that flight MH370 had disappeared at 02:40 local time on Saturday (18:40 GMT on Friday) after leaving Kuala Lumpur.
It had been expected to land in Beijing at 06:30 (22:30 GMT).
Malaysia's transport minister said there was no information on wreckage and he urged against speculation.
"We are doing everything in our power to locate the plane. We are doing everything we can to ensure every possible angle has been addressed," Hishammuddin Hussein told reporters in Kuala Lumpur.
For more than six hours after it was due in, the flight was listed as delayed, but MH370 has now been removed from the international arrivals board.
Friends and relatives expecting to meet passengers from the flight have been instructed to go to a nearby hotel where officials are on hand to provide support and, when it comes, information.
The flight was a code share with China Southern Airlines CZ748 and more than 150 of the 227 passengers on board are Chinese Nationals. State media are reporting that two rescue boats have been sent into the South China Sea, from the ports of Haikou and Nansha, to assist with the search and rescue effort.
The weather along the route from Kuala Lumpur to Beijing was reportedly good and Malaysia Airlines, and the plane, a Boeing 777, both have good safety records.
"Our hope is that the people understand we are being as transparent as we can, we are giving information as quickly as we can, but we want to make sure information has been verified."
Malaysia Airlines chief executive Ahmad Jauhari Yahya said the focus was on helping the families of those missing. He said that 80% of the families had been contacted.
The plane went off the radar south of Vietnam, according to a statement on the Vietnamese government website.
Its last known location was off the country's Ca Mau peninsula although the exact position was not clear, it said.
The Boeing B777-200 aircraft was carrying 227 passengers, including two children, and 12 crew members.
A plane, two helicopters and four vessels have been dispatched by Malaysia to search the seas off its east coast in the South China Sea, the Malaysian Maritime Enforcement Agency was quoted as saying by AFP news agency.
Vietnam also launched a search while the Philippines said it was sending three navy patrol boats and a surveillance plane, AFP adds, and China sent two ships.
The passengers were of 14 different nationalities, Mr Jauhari said.
Among them were 152 Chinese nationals, 38 Malaysians, 12 people from Indonesia and six from Australia.
The pilot was Capt Zaharie Ahmad Shah, 53, who joined Malaysia Airlines in 1981, Mr Yahya said.
A Vietnamese navy official told the BBC the plane had gone missing within Malaysian maritime territory.
Friends and relatives expecting to meet passengers from the flight in Beijing were instructed to go to a nearby hotel where officials were meant to be on hand to provide support.
The Associated Press reported a woman weeping on a shuttle bus who was heard to say on a mobile phone: "They want us to go to the hotel. It cannot be good."
Boeing 777 fact sheet
- Twin-engine jet launched in June 1995
- One of the world's most popular long-distance planes
- Seats between 300 and 380 passengers
- Has flown around five million flights
- Often used for non-stop flights of 16 hours or more
- In September 2001 a crew member died in a re-fuelling fire on a 777 at Denver International Airport
- In 2013 three Chinese women died when the 777 Asiana Flight 214 crashed in San Francisco.